Over the last several years there has been an increasing interest in the role of plasma cholesterol and lipoproteins in the causation of coronary artery disease. Studies regarding the concentrations of plasma cholesterol and triglyceride have received a great deal of publicity regarding their roles in the initiation of atherosclerosis. At high concentrations, these lipids tend to cross arterial cell wall membranes. The cumulative deposition leads to the formation of lipid plaques in the arterial wall which is indicative of an atherosclerotic condition.
Prolactin has recently been shown to have an important role in stimulating the synthesis of lipids in the liver. Suppression of prolactin secretion can block hepatic lipogenesis, and prolactin replacement has fully restored lipogenesis because some of the lipid in the blood is produced in the liver. We believed therefore, that there was a possibility that inhibition of prolactin secretion might also reduce plasma lipids.
Ergot-related prolactin-inhibiting compounds are known and have been administered to vertebrate animals. In U.S. Pat. No. 3,752,814 and U.S. Pat. No. 3,752,888, e.g., 2-bromo-alpha-ergocryptine and certain of its pharmaceutically acceptable acid addition salts and methods for their preparation are described in detail. It is recognized that these compounds are useful in inhibiting lactation, and they exhibit antifertility effects.
In accordance with U.S. Pat. No. 4,659,715 ergot-related prolactin-inhibiting compounds, e.g., 2-bromo-alpha-ergocryptine, are administered to vertebrate animals to decrease body fat stores without concomitant decrease in body weight, and in accordance with U.S. Pat. No. 4,747,709 these compounds are administered to decrease body fat stores, with concomitant loss in body weight.
Despite the considerable usage of the ergot-related prolactin-inhibiting compounds in having been administered in the past to vertebrates for one purpose or another, insofar as known, these compounds have never been viewed as possibly useful for the treatment of atherosclerosis. Various other compounds, or drugs, however, have been employed generally for such purpose; albeit none, insofar as known, have proven entirely satisfactory. One drug of this type is colestipal hydrochloride (Colestid) described in Chapter 21, at Page 224, under "Antilipemics" of "Nurses Guide to Drugs."
There exists a great need, and a tremendous interest by the scientific and medical communities, to develop pharmacological methods for treating vertebrate animals, especially humans, to suppress or to reverse, or both suppress and reverse, the formation of arterial lipid plaques in subjects, or victims to the atherosclerotic condition.